Project Summary/Abstract Point-of-care (POC) testing of clinical samples for the presence of illegal substances and their metabolites is important for monitoring substance use disorders, employment screening, and legal matters relating to drug abstinence. Typical immunoassay screening methods suffer from higher false testing rates and do not provide quantitative information. Confirmatory tests that are used for quantitative analysis rely on chromatographic separations coupled with mass spectrometric (MS) detection, which requires expensive instrumentation and technical expertise for operation. In this research project, a prototype liquid chromatography (LC) instrument with integrated LED-UV detection will be developed for the purpose of POC screening of illicit drugs in clinical samples. The system includes integrated separation column cartridges, which makes column installation much simpler than with traditional instrumentation that requires additional tubing and fittings. A control program that runs on a miniaturized computer with an integrated touch-screen user interface is then used for instrument control and data acquisition. A method library for the separation of different classes of illicit substances will be developed on standard LC instrumentation using a variety of columns packed with different particle types and stationary phase selectivities. These methods will then be translated to the prototype system where users will be able to select a method for a given drug test panel, which reduces the technical expertise required to obtain concentration data on the tested samples. With this instrument, the integrated column cartridge is designed for dual LED-UV detection so that a single analyte is measured at two different absorbance wavelengths to provide positive identification using a new data analysis tool referred to as the ?detection capacity?. The absorbance ratio for a given peak provides qualitative identification, which will ensure that each analyte is accounted for individually during the separation. Potential customers for this new products currently involved in the analysis of illicit substances will collaborate on the project to ensure that the results correlate well with the current methods employed for this application. The results generated by this new system will be faster and provide more analyte information that the standard immunoassay screening tests currently used, providing an important new commercial tool for POC drug monitoring.